The contents of this proposal are based on the observation that, both in vitro and in vivo, the cytotoxicity of some anticancer drugs can be greatly increased if cells are transiently permeabilized, allowing easier passage of the drug, by application of short and intense pulsed electric fields. The objectives and specific aims of this current proposal are to extend the data we have already obtained on tumor regression in animal models with murine melanoma cell lines, by combining bleomycin with electric field. In particular, we will (i) compare different routes of administration, intratumor and intravenous, and investigate the effect of (ii) different dosages, and (iii) multiple treatments, all with bleomycin and optimized electrical parameters. Results of the combination therapy will be compared with three sets of control, namely, no drug and no electric field, and drug or electric field alone. Apart from usual monitoring and observation of the animals, detailed histopathological examinations will also be carried out. In addition, field plots with different geometry of the electrodes, caliper and needles, will be obtained. The long-term aim of the project is to treat human patients with skin cancers, particularly advanced melanoma and basal cell carcinoma by this novel method. PROPOSED COMMERCIAL APPLICATION: The technology will allow treatment of cancer patients using existing anticancer drugs with maximum efficacy. Electroporation-mediated chemotherapy has shown great promise in phase I/II clinical trial of patients with head and neck squamous cell carcinomas.